CE 1: The Respiratory System as a Target for Drug-Induced Toxicity: Pathology and Investigational Techniques

Safety assessment of inhaled therapeutics and chemicals, both industrial and environmental, requires detailed evaluation of the upper respiratory tract along with other standard protocol tissues. Regulatory agencies require the assessment of specific areas of the nasal cavity, larynx, trachea, and lungs in rodent and non-rodent animal models. Although histopathological changes in these organs are well-characterized in the literature, interpretation of their adversity and relevance to man are less clear-cut. The first half of this session will focus on methodologies used to deliver drugs by inhalation and the deposition patterns of inhaled drugs. Presentations on common background and test article-associated changes in different species, and comparative sensitivities of the upper respiratory tract, will cover the histopathological aspects of inhalation studies and their relevance to man. During the second half of the session, the importance of pulmonary macrophages in respiratory health and disease and models used in inhalation studies will be addressed. The final talk will focus on the use of imaging strategies for lung function. This will include MRI, CT, SPECT, PET, and optical modalities, which are being used in the pharmaceutical industry to understand disease in a longitudinal fashion. These modalities increase our understanding of drug delivery and allow discrimination of different aspects of lung pathology, including ventilation deficits, lung perfusion, pulmonary edema, cell migration, and fibrotic lesions.

CE 2: Interpreting and Integrating Clinical and Anatomic Pathology Results: Pulling It All Together

The interpretation of safety findings in toxicology studies requires an integrative weight of evidence approach that takes into account all collected data sets. Data must be evaluated in its entirety, as neither clinical nor anatomic pathology can be relied upon in isolation to fully understand the relationship between study findings and the test article. Basic principles for correlating anatomic pathology and clinical pathology findings and for integrating these with other study endpoints will be reviewed. A series of case examples, presented jointly by a clinical pathologist and an anatomic pathologist, will be used to illustrate the collaborative effort required between clinical and anatomical pathologists. In addition, the diagnostic utility of kidney and liver biomarkers will be discussed, based on data from meta-analyses of preclinical qualification and other studies. Examples of traditional and novel biomarker data implementation in nonclinical toxicology studies will also be presented to illustrate the relationship between discrete changes in biochemistry and tissue morphology in the real world drug development space.

Toxicity involving the hematopoietic system and lymphoid organs is frequently encountered in nonclinical safety studies and represents an important regulatory focus. Clinical pathology and anatomic pathology endpoints have traditionally been used for a first-line assessment of hematotoxicity and immunotoxicity, with additional specialized testing generally performed on a case-by-case basis consequent to study findings or in light of recognized drug class effects. As more specialized techniques including flow cytometry, functional assays, and other novel in vitro evaluations are increasingly utilized, it is important to understand the relationships between these modalities and traditional endpoints, and to be familiar with their advantages and limitations. This session will present comprehensive approaches to the evaluation of hematopoietic and lymphoid organ toxicity and will highlight correlations between non-traditional testing and routine endpoints through didactic presentations and integrated case examples.

CE 4: Is It Adverse, Adaptive, Artifact?

One of the principal challenges of a toxicologic pathologist is to determine and differentiate a true adverse effect from an adaptive response. A number of factors can interfere with a clear, reasoned determination of adversity starting with the lack of consensus on the definition of adversity. In addition, the introduction of artifact, both in poor study design and in histopathology and other data sets can lead to an improper determination of adversity. This CE course will attempt to address these challenges in determining if a finding is adverse or not. The course begins with an overview and position statement from the STP committee on adverse versus adaptive effects and is followed by a discussion on how artifacts and spurious findings can complicate adversity determination. In addition, lectures on determining adverse versus adaptive effects in clinical pathology and the pathology of the digestive system will be given. The course will close with a regulatory perspective on interpreting adverse versus adaptive effects. This CE course is designed to provide practical knowledge with numerous relevant case examples in toxicologic pathology and would be useful to the practicing industrial toxicologic pathologist.

This CE Courses ares approved by the AAVSB RACE to offer a total of 3.50 CE Credits per course (3.50 max) being available to any one veterinarian: and/or 3.50 Veterinary Technician CE Credits (3.50 max). This RACE approval is for the subject matter categorie(s) of:
Category One: Scientific
using the delivery method(s) of: Seminar/Lecture. This approval is valid in jurisdictions which recognize AAVSB RACE; however, participants are responsible for ascertaining each board's CE requirements